Uncle Tom, a slave on the Shelby plantation, is loved by his owners, their son, and every slave on the property. He lives contentedly with his wife and children in their own cabin until Mr. Shelby, deeply in debt to a slave trader named Haley, agrees to sell Tom and Harry, the child of his wife's servant Eliza. Tom is devastated but vows that he will not run away, as he believes that to do so would plunge his master so far into debt that he would be forced to sell every slave.
Just before Tom is taken away, Mrs. Shelby promises him that she will buy him back as soon as she can gather the funds. Tom is sold to Haley, who eventually sells him to a kindly master named Mr. St. Clare. Eliza, however, cannot bear to part with her son and escapes the night before he is to be taken from her. She escapes successfully and makes her way to a Quaker village, with a family that harbors slaves. There, she is reunited with her husband George, who lived on a neighboring plantation and has also escaped to flee his master's cruelty.
The couple and their son spend a night with the Quaker family before returning to the underground railroad. Tom befriends his new master and especially his young daughter Eva, who shares Tom's deep religious faith and devotion. Eva abhors cruelty and eventually is so overcome with grief over slavery that when she becomes ill, she accepts her impending death peacefully and tells her family and their servants that she is happy knowing that she is going to heaven, where such cruelty does not exist. St. Clare begins to confront the realization that he believes slavery is evil, and he promises Tom that he will fill out forms guaranteeing his freedom in the event of St. Clare's death. Shortly after Eva dies, her father dies tragically in an accident, and Tom's fate is left entirely in the hands of Marie, St. Clare's selfish and unsympathetic wife.
Marie decides to move back to her parents' estate and to sell all the slaves, despite Miss Ophelia's exhortation that Marie should fulfill St. Clare's promise to give Tom his freedom. Marie refuses, and just before he is sold, he writes a letter to the Shelbys (with the help of Mr.
Legree) telling them his plight and asking for their help. The letter goes unanswered, and Tom ends up in the hands of Simon Legree, an evil and bitter plantation owner whose philosophy is to work his slaves hard and replace them when they inevitably die just a few years later. On Legree's plantation, Tom meets two fellow slaves, Emmeline and Cassy. Emmeline is a young mulatto woman sold to Legree at the same time as Tom, and she attempts to befriend the embittered Cassy, who has suffered at the hands of Legree for several years.
Cassy has seen her children.